Modern molecular biology has provided us with a means of producing immunogens with unprecedented ease and precision but these new methodologies generate purified immunogens that do not generally induce a strong immune response in the absence of an effective adjuvant. The development of improved vaccine adjuvants for use in humans has therefore become a priority area of research. Nevertheless, research on adjuvants has lagged seriously behind the work done on immunogenes. For decades the only adjuvant widely used in humans has been alum. Saponin and its purified component Quil A, Freund's complete adjuvant and other adjuvants sued in research and veterinary applications have toxicities which limit their potential use in human vaccines. New chemically defined preparations such as muramyl dipeptide and monophosphoryl lipid A are being studied. The Virus Research Institute is interested in the development of vaccines to combat infectious disease. A major focus is the study of delivery systems and adjuvants that will induce a state of systemic immunity. Microencapsulation is the core technology in this endeavor. An area of adjuvant research that has developed over the last few years is the utilization of synthetic polymers such as polylactide-co-glycolide (PLGA) in the formulation of a vaccine to effect the controlled release of antigens. The clear disadvantage of this polymer is the required use of organic solvents that are detrimental to labile antigens. The overall goal of the SBIR Phase I work is to develop a microsphere configured vaccine vehicle based on a water soluble polyphosphazene polymer. This goal will be accomplished by optimizing both the generation of 1-10 micron diameter microspheres for each of five polyphosphazene polymers and determining the does and route to administration that maximize the rapidity, amplitude and duration of the antibody response to a single antigen dose. The distribution of the antibody response over the IgG subclasses and the cellular immune response will be determined. Finally, the protective efficacy of the polyphosphazene microsphere immunization regimen in an animal model will be evaluated.